1. Field Of The Invention
The invention relates to a process for the preparation of optically active piperazine-2-carboxylic acid derivatives, especially esters and amides of (R)- or (S)-piperazine-2-carboxylic acid, which have the general formula: ##STR2## in which X is a hydroxyl group, a C.sub.1-6 -alkoxy group or a group of the formula --NR.sup.1 R.sup.2, in which in turn
(i) R.sup.1 and R.sup.2 independently of one another are hydrogen, C.sub.1-6 -alkyl, C.sub.3-6 -cycloalkyl, aryl or an amino-protecting group, or PA0 (ii) R.sup.1 and R.sup.2, together with the nitrogen atom, form an optionally substituted 5-membered or 6-membered saturated heterocyclic ring, by asymmetric hydrogenation of the corresponding pyrazinecarboxylic acid derivatives. Compounds of this group are valuable intermediates, especially for the preparation of pharmaceutical active substances. Thus, for example, some known compounds, in which X is NH-t-Bu and which have the (S)-configuration, are structural units for HIV protease inhibitors (European Published Patent Application No. 0,541,168). PA0 (i) R.sup.1 and R.sup.2 independently of one another are hydrogen, C.sub.1-6 -alkyl, C.sub.3-6 -cycloalkyl, aryl or an amino-protecting group, or PA0 (ii) R.sup.1 and R.sup.2, together with the nitrogen atom, form an optionally substituted 5-membered or 6-membered saturated heterocyclic ring. The invention process includes asymmetrically hydrogenating a corresponding pyrazinecarboxylic acid derivative of the general formula: ##STR4## in which X is as defined above, in the presence of a catalytically active, optically active rhodium complex.
2. Background Art
Hitherto known syntheses of compounds of the formula I are based on the parent compound (X is OH), which can be obtained in optically active form by conventional resolution of the racemate E. Felder et al., Helv. Chim. Acta, (1960), 43, 888-896!. First, the ring nitrogen atoms are protected and then the free carboxyl group is converted to the amide. At best the process is suitable for the laboratory scale and requires the use of expensive reagents.